Genome-Wide Top2a Dna Cleavage Is Biased Toward Translocated And Highly Transcribed Loci, 2017 University of Pennsylvania
Genome-Wide Top2a Dna Cleavage Is Biased Toward Translocated And Highly Transcribed Loci, Xiang Yu, James W. Davenport, Karen A. Urtishak, Marie L. Carillo, Sager J. Gosai, Christos P. Kolaris, Jo Ann W. Byl, Eric F. Rappaport, Neil Osheroff, Brian D. Gregory, Carolyn A. Felix
Departmental Papers (Biology)
Type II topoisomerases orchestrate proper DNA topology, and they are the targets of anti-cancer drugs that cause treatment-related leukemias with balanced translocations. Here, we develop a high-throughput sequencing technology to define TOP2 cleavage sites at single-base precision, and use the technology to characterize TOP2A cleavage genome-wide in the human K562 leukemia cell line. We find that TOP2A cleavage has functionally conserved local sequence preferences, occurs in cleavage cluster regions (CCRs), and is enriched in introns and lincRNA loci. TOP2A CCRs are biased toward the distal regions of gene bodies, and TOP2 poisons cause a proximal shift in their distribution. We ...
Anxiety Associated Increased Cpg Methylation In The Promoter Of Asb1: A Translational Approach Evidenced By Epidemiological And Clinical Studies And A Murine Model, Rebecca T. Emeny, Jens Baumert, Anthony S. Zannas, Sonja Kunze, Simone Wahl, Stella Iurato
Open Dartmouth: Faculty Open Access Articles
Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n= 1522, age 32–72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders ...
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, 2017 Western University
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, Kevin X. Zhou, Luana Langlois, Ashmita Singh, John Prince
Western Research Forum
Measuring pH is one of the most commonly used techniques in both the laboratory as well as the field due to its importance in a multitude of biochemical processes. Traditional methods of measuring pH may be highly developed in accuracy and precision but often involve disruption of the environment. Biological markers offer an alternative that allows for long-term pH monitoring. This innovative approach allows for vast applications such as in the manufacturing, food processing and research industries. Under moderate acidic conditions, the asr (acid shock RNA) gene is highly inducible and has been demonstrated to be crucial for growth at ...
Is It Time To Start Using Mitochondrial Dna Copy Number As An Indicator Of Health And Diseases?, 2017 Touro College of Osteopathic Medicine (Middletown)
Is It Time To Start Using Mitochondrial Dna Copy Number As An Indicator Of Health And Diseases?, Vasudeva G. Kamath
Touro College of Osteopathic Medicine (Middletown) Publications and Research
The author discusses whether the medical community should seriously investigate the numerical relation of mitochondrial DNA copy number as a health indicator.
Exercise Recommendations For Active Adults At Risk For Sudden Cardiac Death: “Can I Continue To Exercise?”, 2017 University of South Carolina
Exercise Recommendations For Active Adults At Risk For Sudden Cardiac Death: “Can I Continue To Exercise?”, Kacie Lynn Baker
Theses and Dissertations
Sudden arrhythmic death syndrome (SADS) is due to genetic conditions associated with cardiac ion channelopathies and cardiomyopathies. Many of these conditions have exercise guidelines regarding eligibility and disqualification recommendations for competitive athletes through the American Heart Association and the American College for Cardiology. This study investigates how medical professionals communicate these exercise recommendations to patients, and in turn, how well patients understand these recommendations. The study also explores motivations for either continuing or discontinuing an exercise practice after a diagnosis. A questionnaire was distributed through cardiac disease-focused support groups and organizations. Data from 67 individuals with a SADS condition were ...
The Perceived Utility Of Personalized Genomic Medicine In Individuals With A Family History Of Heart Disease: A Pilot Study, 2017 University of South Carolina
The Perceived Utility Of Personalized Genomic Medicine In Individuals With A Family History Of Heart Disease: A Pilot Study, Dana Margaret Mittag
Theses and Dissertations
According to the World Health Organization (2005), cardiovascular disease (CVD) is the number one cause of death in most countries. Assessing a patient’s risk for heart disease may include incorporating factors such as their gender, age, weight, tobacco history, cholesterol, blood pressure, family history, and more recently, genetics. Genome-wide association studies (GWAS) have made it possible to identify risk loci for many of the common, complex disorders, including coronary artery disease (CAD). As the medical genetics community undergoes a shift from a genetics focus to a genomics oriented focus, genomic medicine is becoming more accessible. Research has begun to ...
A Study Of Subthreshold Hallucinatory Experiences And Their Relationship To Genetic Liability For Schizophrenia, 2017 University of Colorado Boulder
A Study Of Subthreshold Hallucinatory Experiences And Their Relationship To Genetic Liability For Schizophrenia, Hannah Young
Undergraduate Honors Theses
One of the hallmarks of schizophrenia is the presence of psychosis. However, subthreshold psychotic symptoms characterized by attenuated delusions and hallucinations also occur in healthy individuals from the general population. A body of evidence suggests that this phenomenon represents a continuum of schizophrenia, with severe and attenuated symptoms sharing a common genetic etiology. Hallucinations are one subthreshold psychotic symptom in which a clear continuum has been observed. The aim of this study is to assess if subthreshold hallucinatory experiences and schizophrenia share genetic liability.
3,028 participants were administered the Launay-Slade Hallucination Scale (LSHS), which measures a predisposition ...
The Autocrine Role Of Proteoglycan-4 (Prg4) In Modulating Osteoarthritic Synoviocyte Proliferation And Expression Of Matrix Degrading Enzymes, Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D. Jay, Khaled A. Elsaid
Pharmacy Faculty Articles and Research
Background: Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)- stimulated conditions.
Methods: Cytosolic and nuclear levels of nuclear factor kappa B (NFκB) p50 and p65 subunits in Prg4+/+ and Prg4-/- synoviocytes were studied using western blot. Nuclear translocation ...
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, 2016 University of New England
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, Meghan May
Biomedical Sciences Faculty Presentations
Dr. Meghan May gives an overview presentation of her research on evolution of virulence and pathogen prediction. The focus of the presentation is a group of organisms called mycoplasmas, and covered subjects include: Mycoplasma synoviae, Mycoplasma gallisepticum, genomic context, predictive modeling, sequence evolution, and genome reduction.
Regulation Of Polycystin-1 Function By Calmodulin Binding, 2016 University of California, Santa Barbara
Regulation Of Polycystin-1 Function By Calmodulin Binding, Nicholas Doerr, Yidi Wang, Kevin R. Kipp, Guangyi Liu, Jesse J. Benza, Vladimir Pletnev, Tengis S. Pavlov, Alexander Staruschenko, Ashraf M. Mohieldin, Maki Takahashi, Surya M. Nauli, Thomas Weimbs
Pharmacy Faculty Articles and Research
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal ...
Investigation Of Genetic Markers In Sub-Elite Australia Rules Football Players, 2016 The University of Notre Dame Australia
Investigation Of Genetic Markers In Sub-Elite Australia Rules Football Players, Ysabel Jacob, Ashley Cripps, Tess Evans, Paola Chivers, Christopher Joyce, Ryan Anderton
Law And The Sciences Of The Brain/Mind, 2016 University of Pennsylvania Law School
Law And The Sciences Of The Brain/Mind, Stephen J. Morse
This chapter is a submission to the Oxford Handbook of Law and the Regulation of Technology edited by Roger Brownsword. It considers whether the new sciences of the brain/mind, especially neuroscience and behavioral genetics, are likely to transform the law’s traditional concepts of the person, agency and responsibility. The chapter begins with a brief speculation about why so many people think these sciences will transform the law. After reviewing the law’s concepts, misguided challenges to them, and the achievements of the new sciences, the chapter confronts the claim that these sciences prove that we are really not ...
Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, 2016 Northwestern Polytechnical University
Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han
Pharmacy Faculty Articles and Research
The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no ...
Transgenerational Epigenetic Effects Of Cocaine On Circadian Behavior And Cocaine Reward, 2016 Kent State University - Kent Campus
Transgenerational Epigenetic Effects Of Cocaine On Circadian Behavior And Cocaine Reward, Victoria Shaker
Undergraduate Research Symposium
Transgenerational Epigenetic Effects of Cocaine on Circadian Behavior and Cocaine Reward
Victoria Shaker, Ashley Shemery, Alex Yaw, & J. David Glass.
Department of Biological Sciences and School of Biomedical Sciences
Professor Glass served as the primary advisor. Ashley Shemery and Alex Yaw served as co-advisors.
Hypothesis: Cocaine irreversibly lengthens circadian period (tau), which could underlie the significant health issues of cocaine addiction. Others have reported that rewarding effects of paternal cocaine use are transgenerational. We hypothesize that the disruptive effects of cocaine on tau may also be transgenerational, causing altered subjective cocaine reward response in offspring (F1).
Methods: Male mice were exposed to cocaine-water (0.5 mg/ml) or water (control) for 6 wks. Immediately following treatment, the mice were mated with cocaine naïve dams. F1 reference for cocaine or sucrose (to test for reward specificity) was analyzed using a dual bottle (water and drug [0.15 mg/ml] or sucrose [2%]) free-choice regimen. Tau was analyzed using activity sensors with computerized data acquisition.
Results and Conclusions: Lengthened tau was evident in sires with forced cocaine compared to controls (24.18+0.17 vs. 24.07+0.02; p0.05). These data reveal that there is no transgenerational transmission of cocaine-lengthened tau in F1 males, but there was an alteration of tau in F1 females. Significantly, paternal cocaine intake significantly altered F1 preference for cocaine, but not sucrose, suggesting specificity to drug reward. Thus, cocaine addiction could involve a transgenerational paternal mode of inheritance.
Keywords: epigenetics, transgenerational, cocaine, sucrose, mice, sex differences, drug abuse, circadian, biological rhythms, addiction
Congenital Stationary Night Blindness In The Dog: Common Mutation In The Rpe65 Gene Indicates Founder Effect, 2016 University of Pennsylvania
Congenital Stationary Night Blindness In The Dog: Common Mutation In The Rpe65 Gene Indicates Founder Effect, Gustavo Aguirre, Victoria Baldwin, Sue Pearce-Kelling, Kristina Narfström, Kunal Ray, Gregory Acland
Gustavo D. Aguirre, VMD, PhD
Purpose: To clone and characterize the canine RPE65 cDNA from normal dog, examine for mutations, and establish if the mutation identified in Swedish briard dogs with retinal dystrophy is present in dogs of the same breed that originated from the United States and other countries, and are affected with congenital stationary night blindness. Methods: Fifteen briard dogs were studied, of which 10 were affected with csnb, and five were clinically normal. In addition, we tested samples from four Swedish dogs, and samples from a briard affected with progressive retinal atrophy. RPE65 cDNA was cloned a from retinal cDNA library by ...
Genetic And Epigenetic Mechanisms Of Complex Reproductive Disorders, 2016 Virginia Commonwealth University
Genetic And Epigenetic Mechanisms Of Complex Reproductive Disorders, Bhavi P. Modi
Theses and Dissertations
Common, complex disorders are polygenic and multifactorial traits representing interactions between environmental, genetic and epigenetic risk factors. More often than not, contributions of these risk factors have been studied individually and this is especially true for complex reproductive traits where application of genomic technologies has been challenging and slow to progress. This thesis explores the potential of genetic and epigenetic components contributing to a better understanding of the biological pathways underlying disease risk in two specific female complex reproductive traits - polycystic ovary syndrome (PCOS) and preterm premature rupture of membranes (PPROM). The PCOS projects focus on characterization of a gene ...
Comorbidity Between Alzheimer’S Disease And Seizure Episodes, 2016 University of Colorado, Boulder
Comorbidity Between Alzheimer’S Disease And Seizure Episodes, Maryam Amini
Undergraduate Honors Theses
A mouse model of Alzheimer’s disease (AD), which overexpress the human amyloid precursor protein (APP), experience Kainic Acid (KA) induced seizures that are more severe than wild type (WT) mice. The latency and severity of seizures observed in AD mice are similar to those of Synaptophysin knockout (Syp KO) mice. Addition of amyloid plaques (Aβ) to cells in vitro leads to the breakdown of Syp-VAMP2 complex. In the present study, we investigated if the breakdown of Syp-VAMP2 complex is responsible for the observed seizure activity in AD mice. The binding of cholesterol to Syp is necessary for biogenesis ...
Molecular Genetics Of Ms4a6a And Alzheimer's Disease, 2016 University of Kentucky
Molecular Genetics Of Ms4a6a And Alzheimer's Disease, Ryan Harpole
Lewis Honors College Capstone Collection
Increased Alzheimer’s disease (AD) risk has previously been associated with a SNP called rs610932 near the gene MS4A6A. The goal of this experiment was to quantify the expression of two MS4A6A isoforms in the brains of AD and non-AD subjects, particularly as a function of rs610932 genotype. According to an article titled “Alzheimer’s Disease Susceptibility Variants in the MS4A6A Gene are Associated with Altered Levels of MS4A6A Expression in Blood”, MS4A6A has four different isoforms that have been reported to be differentially expressed in the blood of AD subjects compared to non-AD subjects (Petroula et al., 2014). After ...
Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, 2016 University of Central Florida
Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, Brian V. Skibo
Honors in the Major Theses
The purpose of this thesis is to examine familial hypercholesterolemia (FH) and emerging pharmacogenomics therapies that propose to lower serum low density lipid (LDL) levels. The search of various data bases resulted in nine research articles being selected for review. Syntheses of the articles suggest emerging phamacogenomic drug therapy can improve treatment outcomes for individuals with a diagnosis of FH. The Human Genome Project (HGP) has had far reaching applications for genomic technologies and pharmacagenomic interventions, tailored to human conditions associated with select genomic traits. Synthesis of nine research articles demonstrate that little is known on the topic and reveals ...
The Anti-Inflammatory Caspase-12 Gene Does Not Influence Sle Phenotype In African-Americans, 2016 Touro University California
The Anti-Inflammatory Caspase-12 Gene Does Not Influence Sle Phenotype In African-Americans, Trista Fuchs, Jennifer A. Kelly, Emily Simon, Kathy L. Sivils, Evan Hermel
College of Osteopathic Medicine (TUC) Publications and Research
No abstract provided.